Orexin and Alzheimer's Disease

Alzheimer's disease (AD) is the most frequent age-related dementia. It prevalently causes cognitive decline, although it is frequently associated with secondary behavioral disturbances. AD neurodegeneration characteristically produces a remarkable destruction of the sleep–wake cycle, with diurnal napping, nighttime arousals, sleep fragmentation, and REM sleep impairment. It was recently hypothesized that the orexinergic system was involved in AD pathology. Accordingly, recent papers showed the association between orexinergic neurotransmission dysfunction, sleep impairment, and cognitive decline in AD. Orexin is a hypothalamic neurotransmitter which physiologically produces wakefulness and reduces REM sleep and may alter the sleep–wake cycle in AD patients. Furthermore, the orexinergic system seems to interact with CSF AD biomarkers, such as beta-amyloid and tau proteins. Beta-amyloid accumulation is the main hallmark of AD pathology, while tau proteins mark brain neuronal injury due to AD pathology. Investigations so far suggest that orexinergic signaling overexpression alters the sleep–wake cycle and secondarily induces beta-amyloid accumulation and tau-mediated neurodegeneration. Therefore, considering that orexinergic system dysregulation impairs sleep–wake rhythms and may influence AD pathology, it is hypothesized that orexin receptor antagonists are likely potential preventive/therapeutic options in AD patients

222Rn daughters influence on scaler mode of the ARGO-YBJ detector

The ARGO-YBJ experiment is a full coverage air shower array; its lowest energy threshold is reached using the "scaler mode technique". Working in this mode, the signals generated by any particle hitting each cluster are put in coincidence every 150 ns and read by four independent scaler channels, giving the counting rates of multiplicity \geq1, \geq2, \geq3 and \geq4 (C1, C2, C3 and C4, respectively). The study of these counting rates pointed out a different behaviour of C1 respect to C2, C3 and C4, suggesting that C1 is detecting not only cosmic rays. This work shows that the radon (222Rn) gamma emitter daughters present in the ARGO-YBJ building air are contributing to C1 counts at the level of 1 Hz each Bq/m3 of radon. The uncertainty about this contribution is great, because of the high variability of 222Rn concentration and the building ventilation. The radon monitoring will allow the C1 correction improving the sensitivity of the ARGO-YBJ experiment at its lowest energy threshold.Comment: 4 pages, 3 figures, Proceedings of the 32nd International Cosmic Ray Conference (ICRC

On the effect of foaming agents on the porous structure and zeolite content of ceramic foams produced by geopolymer gel conversion

Please click Additional Files below to see the full abstract

Is there something new under the sun?

The growing number of patients with obstructive sleep apnea is challenging healthcare systems worldwide. Obstructive sleep apnea is characterized by chronic intermittent hypoxaemia, episodes of apnea and hypopnea, and fragmented sleep. Cardiovascular and metabolic diseases are common in obstructive sleep apnea, also in lean patients. Further, comorbidity burden is not unambiguously linked to the severity of obstructive sleep apnea. There is a growing body of evidence revealing diverse functions beyond the conventional tasks of different organs such as carotid body and gut microbiota. Chronic intermittent hypoxia and sleep loss due to sleep fragmentation are associated with insulin resistance. Indeed, carotid body is a multi-sensor organ not sensoring only hypoxia and hypercapnia but also acting as a metabolic sensor. The emerging evidence shows that obstructive sleep apnea and particularly chronic intermittent hypoxia is associated with non-alcoholic fatty liver disease. Gut dysbiosis seems to be an important factor in the pathophysiology of obstructive sleep apnea and its consequences. The impact of sleep fragmentation and intermittent hypoxia on the development of metabolic syndrome may be mediated via altered gut microbiota. Circadian misalignment seems to have an impact on the cardiometabolic risk in obstructive sleep apnea. Dysfunction of cerebral metabolism is also related to hypoxia and sleep fragmentation. Therefore, obstructive sleep apnea may alter cerebral metabolism and predispose to neurocognitive impairment. Moreover, recent data show that obstructive sleep apnea independently predicts impaired lipid levels. This mini-review will provide novel insights into the mechanisms of metabolic dysfunction in obstructive sleep apnea combining recent evidence from basic, translational and clinical research, and discuss the impact of positive airway pressure treatment on metabolic disorders.publishersversionpublishe

Effects of melatonin prolonged-release on both sleep and motor symptoms in Parkinson's disease: a preliminary evidence

background sleep-related symptoms, especially insomnia, are frequently reported by patients with parkinson's disease (PD) and can markedly affect motor symptoms and impair patients' quality of life. melatonin has been shown to improve sleep in PD patients. this pilot study aimed at evaluating the effects of a 3-month treatment with 2 mg melatonin prolonged-release (PR) on sleep and motor disability in PD patients. materials and methods twelve PD patients under stable antiparkinsonian treatment were enrolled in the study. before treatment (T0), motor dysfunction was assessed with unified parkinson's disease rating scale (UPDRS-III) and sleep architecture with polysomnography. subjective sleep quality was also assessed through pittsburgh sleep quality Index (PSQI) and daytime somnolence with epworth sleepiness Scale (ESS). patients then started melatonin PR and all measures were repeated at the end of treatment after 3 months (T1). results sleep latency significantly decreased from T0 to T1, but no other significant differences were found in PSG parameters. melatonin PR treatment significantly reduced the ESS scores from T0 to T1, while the PSQI scores presented a trend of improvement from T0 to T1. motor dysfunction was not improved by melatonin PR, although there was a trend in decreasing UPDRS-III. both clinical global improvement and patient clinical global impression documented an improvement in insomnia symptoms at T1. conclusions these findings suggest that melatonin may improve sleep symptoms in PD patients, although further evidence is needed in larger controlled studies to confirm these results and explore the possible direct and indirect influence of sleep improvement on motor dysfunction

PERMIT study: a global pooled analysis study of the effectiveness and tolerability of perampanel in routine clinical practice

Effectiveness; Focal epilepsy; TolerabilityEficacia; Epilepsia focal; TolerabilidadEficàcia; Epilèpsia focal; TolerabilitatThe PERaMpanel pooled analysIs of effecTiveness and tolerability (PERMIT) study was a pooled analysis of data from 44 real-world studies from 17 countries, in which people with epilepsy (PWE; focal and generalized) were treated with perampanel (PER). Retention and effectiveness were assessed after 3, 6, and 12 months, and at the last visit (last observation carried forward). Effectiveness assessments included 50% responder rate (≥ 50% reduction in seizure frequency from baseline) and seizure freedom rate (no seizures since at least the prior visit); in PWE with status epilepticus, response was defined as seizures under control. Safety and tolerability were assessed by evaluating adverse events (AEs) and discontinuation due to AEs. The Full Analysis Set included 5193 PWE. Retention, effectiveness and safety/tolerability were assessed in 4721, 4392 and 4617, respectively. Retention on PER treatment at 3, 6, and 12 months was 90.5%, 79.8%, and 64.2%, respectively. Mean retention time on PER treatment was 10.8 months. The 50% responder rate was 58.3% at 12 months and 50.0% at the last visit, and the corresponding seizure freedom rates were 23.2% and 20.5%, respectively; 52.7% of PWE with status epilepticus responded to PER treatment. Overall, 49.9% of PWE reported AEs and the most frequently reported AEs (≥ 5% of PWE) were dizziness/vertigo (15.2%), somnolence (10.6%), irritability (8.4%), and behavioral disorders (5.4%). At 12 months, 17.6% of PWEs had discontinued due to AEs. PERMIT demonstrated that PER is effective and generally well tolerated when used to treat people with focal and/or generalized epilepsy in everyday clinical practice.This study was funded by Eisai Ltd. Editorial assistance in the preparation of this manuscript was funded by Eisai Ltd

Perampanel outcomes at different stages of treatment in people with focal and generalized epilepsy treated in clinical practice: Evidence from the PERMIT study

Effectiveness; Focal epilepsy; PerampanelEficacia; Epilepsia focal; PerampanelEfectivitat; Epilèpsia focal; PerampanelIntroduction: The PERMIT study is the largest pooled analysis of perampanel (PER) clinical practice data conducted to date. Methods: This post-hoc analysis of PERMIT investigated the effectiveness, safety and tolerability of PER when used as early add-on therapy (after failure of one or two previous antiseizure medications) in comparison with late add-on therapy (after failure of three or more previous antiseizure medications). Retention and effectiveness were assessed after 3, 6, and 12 months, and at the last visit (last observation carried forward). Effectiveness was assessed by seizure type (total seizures, focal seizures, generalized tonic-clonic seizures [GTCS]) and assessments included seizure freedom rate and responder rate. Safety and tolerability were assessed by evaluating adverse events (AEs) and discontinuation due to AEs. Results: The Full Analysis Set included 1184 and 2861 PWE treated with PER as early and late add-on therapy, respectively. Compared to the late add-on subgroup, the early add-on subgroup was characterized by later mean age at epilepsy onset, shorter mean duration of epilepsy, lower rates of intellectual disability and psychiatric comorbidity, and lower frequency of seizures per month, suggesting a less severe form of epilepsy in this subgroup. After 12 months, retention was significantly higher in the early versus late add-on subgroup (67.7% vs. 62.4%; p = 0.004). At the last visit, responder rates in the early versus late add-on subgroup were significantly higher for total seizures (68.2% vs. 39.3%; p < 0.001), focal seizures (65.0% vs. 36.8%; p < 0.001) and GTCS (83.7% vs. 67.2%; p < 0.001), as were seizure freedom rates (total seizures, 35.9% vs. 11.9% [p < 0.001]; focal seizures, 29.4% vs. 8.7% [p < 0.001]; GTCS, 69.0% vs. 48.1% [p < 0.001]). Incidence of AEs was significantly lower in the early versus late add-on subgroup (42.1% vs. 54.7%; p < 0.001), as was the rate of discontinuation due to AEs over 12 months (15.0% vs. 18.1%; p = 0.031). Discussion: This study demonstrated that PER was effective and generally well tolerated when initiated as early or late add-on therapy, but it was significantly more effective and better tolerated when initiated early. These findings support PER's use as a broad-spectrum, early add-on therapy for use in PWE with focal and generalized seizures.The study received funding from Eisai Ltd. Editorial assistance was provided by John Scopes of mXm Medical Communications and funded Eisai Ltd

Osteoporosis guidelines from a rehabilitation perspective: systematic analysis and quality appraisal using AGREE II

Background: People affected by osteoporosis and fragility fractures often report disability and poor health-related quality of life. Albeit rehabilitation has a crucial role in older people, post-menopausal women and other subjects with high risk of fragility fractures, the rehabilitation perspective has been poorly investigated in the available guidelines for osteoporosis. Aim: To systematically evaluate the quality of guidelines for osteoporosis from a rehabilitation perspective. Design: Systematic analysis of guidelines. Setting: Not applicable. Population: Osteoporotic patients. Methods: On May 2020, we performed a systematic search on medical literature of all guidelines published in the last 10 years on PubMed, PEDro, and international guideline databases. The study selection was based on key terms "exercise", "physical activity" or "rehabilitation". All authors independently assessed the methodological quality through the Appraisal of Guidelines for Research &amp; Evaluation (AGREE) II instrument, consisting of six domains (scope, stakeholder involvement, rigor and development, clarity of presentation, applicability, editorial independence). Results: Out of 331 documents retrieved, a total of 34 guidelines were selected after the screening phases. Twenty (58.8%) high quality guidelines were reported. According to AGREE II instrument, a mean score of 78.1±21.8% was reported for "scope and purpose" domain; for stakeholder involvement, the mean score was 58.1±22.1%; the rigor of development was good (mean score of 61.3±27.3%); for clarity of presentation the mean score was 79.4±20.3%; the applicability was poor (mean score of 30.9±25.2%); for editorial independence the mean score was 75.1±24.6%. Rehabilitation recommendations for osteoporotic patients were reported in 21 (61.8%) of the selected guidelines. Conclusions: This is the first systematic analysis evaluating quality of the guidelines for osteoporosis using AGREE II instrument. Starting from a state of the art of the currently available evidence, we could conclude that therapeutic exercise at moderate to high intensity is encouraged by several guidelines for the management of people with osteoporosis and fragility fractures. More than half of guidelines were of high-quality. However, most guidelines are lacking specific indications about exercise features. Clinical rehabilitation impact: This study might support the implementation of a rehabilitation perspective in the guidelines for osteoporotic patients

Assessment of Psychometric Characteristics of Parkinson’s Disease Sleep Scale 2 and Analysis of a Cut-Off Score for Detecting Insomnia in Italian Patients with Parkinson’s Disease: A Validation Study

introduction: sleep disorders are frequent non-motor symptoms affecting patients with parkinson's disease (PD). Insomnia represents the most common sleep disorder. parkinson's disease Sleep Scale 2 (PDSS-2) is a specific tool to investigate sleep problems in PD. the general sleep disturbances scale (GSDS) was a general scale validated for the Italian population. our goal was to assess the psychometric characteristics of PDSS-2 and the GSDS in this population, calculating a cut-off score for insomnia symptoms by using subitems of PDSS-2. methods: patients admitted at the PD unit of the hospital of rome tor vergata outpatient clinic and those afferent to PD associations were asked to complete PDSS-2 and GSDS to be correlated to identify a cut-off for insomnia symptoms. Items 1,2,3,8,13 of PDSS-2 were used to detect insomnia. an ROC curve to assess a cut-off score for insomnia was determined. a cross-cultural analysis of PD population characteristics was performed. results: In total, 350 PD patients were recruited. cronbach's alpha was high for the total score (0.828 for PDSS-2 and 0.832 for GSDS). a cross-cultural analysis did not show any significant p-value. the ROC curve yielded an AUC of 0.79 (CI: 0.75-0.84). the cut-off value for insomnia disorder based on items 1,2,3,8,13 of PDSS-2 was &gt;10, demonstrating a sensitivity of 76% and a specificity of 69% in determining the presence of subjective insomnia symptoms in PD. discussion: PDSS-2 is demonstrated to be a valid, specific tool to address sleep disturbances in PD patients. a cut-off score of 10 for items 1,2,3,8,13 was identified for detecting insomnia symptoms in PD patients